Synthesis of 6-Ethoxy-4-(Ureido) Indole-3-Sulfonic Acid and its Computational Evaluation against Prostate Cancer

This research focused on developing a new prostate cancer drug to overcome the side effects and
resistance associated with current therapies like Olaparib. The study leveraged the indole moiety,
a scaffold renowned for its favourable pharmacokinetic properties in anticancer drug
development, to synthesise a new compound: 6-ethoxy-4-(ureido)indole-3-sulfonic acid. A three-
step synthetic route was employed, starting with the sulfonation of indole, followed by
regioselective C-4 ureidation with urea and culminating in ethoxylation using sodium ethoxide.
The final product was purified via vacuum liquid chromatography and its chemical structure was
confirmed through characterisation using FT-IR and NMR spectroscopy. The FT-IR spectrum
showed critical absorptions for N-H stretching (3431.83, 3337.16, 3260 cm⁻¹) and the C=O of
the ureido amide (1676.5 cm⁻¹). Furthermore, the 1 H NMR spectrum displayed resonances for

the ethoxy protons at 3.81 ppm, while the 13 C NMR spectrum confirmed eleven carbons,
including the key ureido-substituted carbon at C-4 (148–157 ppm). The compound's potential
was then evaluated through in-silico methods. Molecular docking studies against the PARP
enzyme (PDB ID: 3L3M) demonstrated that the novel indole derivative possessed an enhanced
binding affinity and formed more interactions with the target protein compared to Olaparib.
Also, ADME-Toxicity (Absorption, Distribution, Metabolism, Excretion and Toxicity) analysis
predicted favourable pharmacokinetics. Based on these in-silico results, which demonstrate
promising drug-like properties, the study strongly recommends further investigation and
development of this synthesised indole derivative as a leading candidate for the treatment of
prostate cancer.

Prostate cancer, poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, ADME-T analysis.

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